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PubMed · 1759942

Increased generalization between drug-related interoceptive stimuli with delayed testing.

Abstract

Although the flattening of generalization gradients over time has been widely investigated using exteroceptive stimuli, little attention has been given to generalization involving interoceptive stimuli. To investigate generalization between internal states, Sprague-Dawley rats were given either 0.835 ml/kg chloropent or 15 mg/kg sodium pentobarbital. Both drugs produced asymmetrical state-dependent retention of a passive avoidance response, that is, good retention in the "same state" conditions (i.e., the drug-drug and no drug-no drug conditions) as well as in the no drug-drug conditions but poor retention in the drug-no drug conditions, at both 1- and 7-day retention intervals. Furthermore, subjects trained in one drug state (pentobarbital or chloropent) demonstrated disrupted performance when tested 1 day later in another drug state, but good performance when tested 7 days later in the other drug state, indicating a decrement in the discriminability of the two drug states after 7 days. This outcome demonstrates that generalization gradients between drug states flatten over time. Moreover, these results suggest that memory for attributes of internal stimuli undergoes changes similar to those found for exteroceptive stimuli. Implications for contextual cues models of forgetting are considered.

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BibTeXRIS

E A MacArdy, D C Riccio. 1991. Increased generalization between drug-related interoceptive stimuli with delayed testing.. https://doi.org/10.1016/0163-1047(91)90608-s

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Barbiturates were introduced into medical practice in 1934. They are widely used today as general anesthetics. Although in vitro studies revealed that the activity of a variety of ligand-gated channels is modulated by barbiturates, the target(s) mediating the anesthetic actions of barbiturates in vivo are unknown. Studying pentobarbital action in beta3(N265M) mice harboring beta3-containing GABAA receptors insensitive to a variety of general anesthetic agents, we found that the immobilizing action of pentobarbital is mediated fully, and the hypnotic action is mediated in part by this receptor subtype. It was surprising that the respiratory depressant action of pentobarbital is indistinguishable between beta3(N265M) and wild-type mice and thus is mediated by other as-yet-unidentified targets. Whereas the target for the immobilizing and hypnotic actions of pentobarbital seems to be the same as for etomidate and propofol, these latter agents' respiratory depressant actions are mediated by beta3-containing GABAA receptors. Thus, in contrast to etomidate and propofol, pentobarbital can elicit respiratory depression by a beta3-independent pathway. Pentobarbital reduced heart rate and body temperature to a slightly smaller extent in beta3(N265M) mice compared with wild-type mice, indicating that these actions are largely mediated by other targets. Pentobarbital-induced increase of heart rate variability and prolongation of ECG intervals are seen in both beta3(N265M) mice and wild-type mice, suggesting that they are not dependent on beta3-containing GABAA receptors. In summary, we show a clear pharmacological dissociation of the immobilizing/hypnotic and respiratory/cardiovascular actions of pentobarbital.

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